The Biocompatibility Research Of China Made Carbon Fibers Reinforced Polyetheretherketone

7 Metal fixators commonly used by clinical orthopedic surgeons as medical instruments are mainly made of titanium alloy and stainless steel. Due to their intensity, they can well provide instant stability to the fracture and therefore are widely applied and considered a gold standard in the field. Many shortcomings, however, are spotted in metals fixators, which necessitate the search for a substitute, non-metal, low in cost and elastic modulus, and high in rigidity.Absorbable nonmetal materials first raised wide concern due to its low elastic modulus when used as internal fixation materials. Research shows that absorbable nonmetal materials have better performance than metal materials concerning curative effect, though its degradation speed and histological reaction resulted from its degradation product narrowed its use in clinical domain.PEEK, engineering plastic invented recently, with its outstanding material characteristics and high biocompatibility is being experimented clinically, although it shows unsatisfying characteristics in strength and hence is limited in practical use. CFR/PEEK, as a compound from PEEK, demonstrates enhanced strength and widened scope of application. This paper deals with the clinical performance of CFR/PEEK as against that of titanium alloy, concerning their respective biocompatibility, to decide a better substitute of metal internal fixation materials。Chapter One Evaluation on Materials'BiocompatibilityMaterials'biocompatibility is defined as the ability of materials to accommodate to adjacent tissue, cell, cell organ, and biomacromolecule, while avoiding thromb, inflammation, toxic reaction, allergy, canceration and other biorejection reaction. This ability is a prime concern for researchers dealing with medical high polymer as internal fixation materials, which includes blood compatibility and histocompatibility.Section One Blood CompatibilityBlood compatibility refers to the ability of materials to form thromb on its surface and its effect on hemolytic crisis, degraded function of platelet, temporary reduction and defection of leucocyte, the activation of complement and the like.There exist three kinds of experiment: In vitro, Ex vivo and Invivo ones.Materials'effects on blood are mainly: ①To activate the blood pathway of clotting, to activate platelet, and to form thromb,②To arouse haemolysis when components in materials work on blood cell,③To cause leukocyte chemotaxis, accumulation, and activation due to extraneous stimulation from high polymer material.1 Thromb occur where materials contact bloodAs a result of the interaction of material and blood, thromb occur shortly after the implanted foreign materials contact blood, which relates to plasma protein, blood coagulation factor, platelet and other components in blood.1.1 Evaluation on Materials'Ability and Amount of Protein Adsorption1.1.1 Materials'Ability of Protein Adsorption Protein adsorption is proved to result from the interaction of material and blood, occurring on the surface where materials contact blood. Therefore the surface character is a key factor that affects protein adsorption.Surface tension, a key index to measure materials'surface character, is highly valued by researchers. According to research done, the greater the polar-component and the smaller the nonpolar-component, the worse the blood compatibility.Contact angle measurement is mainly adopted to get the surface tension. By using Video-optical Contact Angle Measuring Instrument, we can get the contact angle of reagents and materials, after which process, Young's equations can be applied to get the surface tension, nonpolar-component and polar-component.According to our measurement of the surface tension and polar-component of titanium alloy, china-made PEEK and china-made CFR/PEEK, their surface tension values are PEEK>CFR/PEEK> titanium alloy, and their polar-component values are PEEK> titanium alloy >CFR/PEEK. Hence, conclusion can be drawn that CFR/PEEK shows better performance than PEEK and titanium alloy, and also equivalent blood compatibility to that of titanium alloy.1.1.2 The Amount of Plasma Protein Adsorption on Materials'SurfacePlasma protein adsorption occurs first when materials contact blood, in which the adsorbed protein layer triggers a series of reaction. Therefore, the component and conformation of this layer decide the ability of protein adsorption.When materials contact blood, the types of plasma protein absorbed are related to the amount of platelet adherence. Albumen absorbs fastest among all the substances in plasma protein, and hence decides the irreversible protein adsorption.Two ways of evaluation are adopted currently, experiment of protein adsorption and monitoring the amount of plasma protein change. Through test, no obvious difference in influence on plasma protein can be detected between the china-made CFR/PEEK and titanium alloy.1.2 The Change of Platelet from Contact of Material1.2.1 Platelet aggregation and adhesionWhen materials contact blood, a protein layer will occur on the surface, and platelet aggregation and adhesion will ensue resulting in the change of its form. Electron microscope can be adopted to monitor the form of platelet, from which the degree of form change can be decided by using appearance index. The less change the absorbed platelet shows and the smaller the appearance index, the better the blood compatibility.1.2.2 The Activation of Platelet from Contact of MaterialBefore platelet aggregation and adhesion, platelet gets activated, and characteristic marker molecules occur in the activated platelet. Thus, by monitoring these marker molecules, we can well monitor materials'blood compatibility.CD62p and CD63 exist on the surface of irreversible activated platelet, through which we can decide the degree of platelet activation.By measuring the amount of CD62p and CD63 in the contacted blood of titanium alloy and of china-made CFR/PEEK, and by deciding their respective degrees of platelet activation, their respective effects on platelet can be compared. And a conclusion can be drawn that no obvious difference in influence on platelet can be detected between the china-made CFR/PEEK and titanium alloy.2 materials'impacts on akaryocyte and leucocyte2.1 materials'impacts on akaryocyteAfter contacting the blood, the materials may cause the hemocytolysis to the akaryocyte.Due to the changes in the akaryocyte caused by the materials, hemocytolysis experiment has always been adopted as the evaluation method. hemocytolysis experiment is one of the basic methods to test the mutual impacts between the materials and akaryocyte, evaluate in vitro acute haematolysis, and identify blood biocompatibility. It can also clearly reflect the test piece's impact on akaryocyte.Currently, direct measurement of free hemoglobin, in other word, haematolysis rate measurement, is widely used to evaluate the materials haematolysis both home and abroad. The haematolysis rate of test piece should be less than 5%, if not , it means that the material is effective in haematolysis.By testing the haematolysis rate of titanium and domestic CFR/PEEK, and the changes in the number of akaryocyte in the blood due to the contact to these two materials, these two materials'impacts on akaryocyte could be reflected. According to the experiment statistic, the haematolysis rate of titanium and domestic CFR/PEEK are less than 5%, moreover there is no noticeable difference between the two; there is also no notable difference in the materials'impacts on the number of akaryocyte.2.2 materials'impacts on leucocyteAlmost all the materials are able to activate the neutrophil and histoleucocyte. When leucocyte is activated, the main manifestation is the level of CD11/CD18中CD11b/CD18 would be raised, and the expression of tissue factor.The flow cytometry which tests the marked leucocyte activation CD11b/CD18 level, is usually adopted to test the leucocyte activation level. The method could directly tell the leucocyte activation level。Through testing the changes of the content and the leucocyte number in CD11b/CD18, caused by the contact of titanium and domestic CFR/PEEK, the two materials'impacts on leucocyte could be reflected. The experiment statistics show that there is no noticeable difference in the two materials'impacts on leucocyte.3 materials'impacts on blood complement systemComplement system is composed of over 20 complement elements. Research found that the high polymer materials which have amino, hydroxyl, and acidity group on the surface, would usually lead to complement activation, while contacting to the blood.At present, level measurements of blood-serum C3,C4 are adopted to evaluate the materials'impacts on blood complement system.The statistics, drawn from the testing of the content in complementC3,C4, after the contacting titanium alloy and domestic CFR/PEEK to the blood, indicate that, there is no noticeable difference in the two materials'impacts on complement.Section Two Materials HistocompatibilityThe materials histocompatibility refers to the contact of materials to the organism, but it won't cause acute or chronic general reaction, such as throm, acute inflammation, and canceration etc.. It has no stimulation to tissue, and is able to keep the normal function of organism without rejection.The materials histocompatibility is mainly composed by two parts:1. cytotoxicity 2. local reaction after implantation.1 materials cytotoxicity 1.1 evaluation criterion of cytotoxicityTaking the advantage of effective evaluation measure and adopting the qualitative or quantitative methods to test the cytotoxicity, is major means to evaluate the materials cytotoxicity.1.2 Selecting the cell lineWhen select the cell line, researchers would usually take the cell line which is recommended by the international organization, while combine the related primary cell. The toxicity result of primary cell could be a better proof of the clinical effect of materials, and boasts more significance to clinic.1.3 methods of materials cytotoxicity experimentIn vitro cell culture method is mainly used in materials cytotoxicity experiment. The methods used in cytotoxicity experiment include experiment method , contact method and indirect contact method.2 local reaction after implantation of materialsThe evaluation of internal fixation materials histocompatibility in orthopaedic surgery focuses on two aspects:①soft tissue compatibility;②bone compatibility2.1 selection of animal models and design of test pieceAfter the materials are implanted, foreign body reaction will appear, which leads to the inflammatory reaction. Animal in vivo experiment is the essential part in the evaluation of materials histocompatibility.The selection of experimental animal will be made according the size of implant test piece, experiment cycle, animal life period and the bioreaction differences between sclerous tissues and soft tissues among genus.Shape design principle of implant test piece is easy to plant and easy to observe, in line with the experiment content.2.2 implant place and amountImplant the test piece into the subcutaneous tissue or muscle of the experimental animal. The accurate place of the implant test piece has not been defined yet. From the perspective of convenience for observation and the size of tissue area, most researcher often implant it into the subcutaneous tissue in the animal's back, or in its muscle.2.3 evaluation methods and contentsThrough the macroscopic observation of different periods, grading the histopathology experiment reaction and recording, the bioreaction could be evaluated, coupled with comparing the bioreaction between experiment materials and compare materials. The cut organization sample should include the implant and the unaffected surrounding tissues as many as possible.The author chooses HFOB1.19,HSF,and NIH3T3,and adopts CCK-8 method to measure the cell multiplication and cytotoxicity. The experiment indicts that there is no notable differences among the impacts of these two materials on the three cells, and the cell compatibility are very good.Implant the titanium alloy and domestic CFR/PEEK test piece into the rabbit. Take out the materials and the surrounding tissue in the 1st, 2nd, 4th, 8th, 16th, 24th and 48th weeks, and observe the impacts of these two materials on the rabbit's soft tissue and bone tissue. The result shows that there is no notable difference of the two materials'impact on the surrounding tissue.A series experiments reveal that, the blood compatibility and histocompatibility of domestic CFR/PEEK and titanium alloy are the same. It proves that domestic CFR/PEEK has excellent biocompatibility, and it is a novel and safe nonmetal implant materials, which could take the place of titanium alloy to be made into internal fixtor for humans.